Lung cancer (LC) is a leading cause of cancer deaths in the U.S. The widespread adoption of computed tomography (CT) screening enables the early detection of lung cancer and is expected to increase the number of long-term LC survivors. The estimated number of LC survivors is approximately 412,230 as of 2012 and is projected to be over a half million in 2022. Recent studies show that LC survivors have a high risk of developing second primary lung cancer (SPLC), the incidence of which is around 4-6 times higher than that of initial primary lung cancer (IPLC) in the general population. While national lung screening guidelines have been established for IPLC by the U.S. Preventive Services Task Force (USPSTF), no such consensus guidelines exist for LC survivors who are exposed to a high risk of SPLC. Furthermore, the factors that contribute to the development of SPLC have not yet been established. Our long-term goal is to reduce the overall LC mortality in the U.S. population by focusing on SPLC. The overall objectives of this application are to identify the genetic, clinical, and environmental determinants for SPLC, to assess an individual?s risk of developing SPLC, and to evaluate efficient lung screening strategies for SPLC to help inform the development of consensus screening guidelines for LC survivors. Our aims are: (AIM 1) To identify the genetic, environmental, clinical, and demographic risk factors for SPLC and to develop a risk prediction model for SPLC. We will use cohort data from the Transdisciplinary Research in Cancer of the Lung (TRICL) and the International Lung Cancer Consortium (ILCCO) to evaluate risk factors for SPLC; (AIM 2) To evaluate optimal CT screening strategies for SPLC by estimating the population-level harms and benefits of CT screening under various selection criteria. We will develop a stochastic simulation model for SPLC that integrates the incidence, progression, and survival of SPLC to quantify the population-level harms and benefits of screening for SPLC under various risk- based selection criteria; (AIM 3) To estimate the lifetime costs and to assess the cost-effectiveness of CT screening strategies for SPLC in the general U.S. population. The contribution of our research will be significant because it will provide a better understanding of the etiology of SPLC by identifying various risk factors for SPLC using comprehensive population-based data. Second, the completion of our research will provide a valuable decision tool for evaluating an individual?s risk of developing SPLC, which can help identify high-risk individuals for screening. Finally, by evaluating the potential harms and benefits of lung cancer screening for SPLC under various criteria, our research will provide a set of optimal CT screening strategies, the results of which will reduce clinicians? uncertainty on how to best guide LC survivors for CT screening.